‘Don’t dismiss the patient’: Promises, pitfalls of at-home hormone testing
At-home medical testing, ranging from cancer screening to COVID-19 detection, may be transforming health care, but some direct-to-consumer hormone test kits have raised red flags for endocrinologists.
Experts who spoke with Endocrine Today noted that home testing is not new in endocrinology, with blood glucose monitoring and home collection of saliva cortisol samples serving as mainstays of management for diabetes and Cushing’s syndrome, respectively. The issues with direct-to-consumer (DTC) tests, they noted, boil down to the substantial variation in standards and the absence of physician involvement.
“I’m not opposed to at-home hormone testing using Clinical Laboratory Improvement Amendments (CLIA)-approved, legitimate testing venues,” Richard J. Auchus, MD, PhD, professor of pharmacology and internal medicine at the University of Michigan, told Endocrine Today. “There is a big role for at-home testing, like we have been doing with glucose for a long time, but it has to be done correctly. It’s not quite ready for prime time.”
Even so, these at-home tests, including DTC kits, may eventually have a place in the management of endocrine conditions and therefore require more nuanced consideration by physicians, according to Mihail Zilbermint, MD, MBA, FACE, associate professor of clinical medicine at The Johns Hopkins School of Medicine and chief and director of endocrinology, diabetes and metabolism at Suburban Hospital in Bethesda, Maryland.
“I never encourage patients to use these tests, but I personally believe that this is part of the future of access to endocrinologists and treating hormonal conditions,” Zilbermint told Endocrine Today. “We as physicians have to become more familiar with these ... so we can properly counsel our patients.”
Questions about quality
DTC at-home test kits vary substantially in terms of the hormones tested, sample collection and analysis, and physician interpretation. Generally, though, manufacturers offer a number of different panels that screen for specific conditions, such as infertility, thyroid disease, hypogonadism or low testosterone, or “adrenal fatigue,” as well as broader categories, including general metabolic wellness or women’s health.
Each kit measures different combinations of hormones and biomarkers, with some evaluating as many as 11 biomarkers in one test, using saliva or blood collected via finger stick. Consumers then mail the samples to a laboratory and receive the results in several days. Some tests also offer sample collection in a lab setting.
This model raises several questions, according to Hershel Raff, PhD, FAAAS, FAPS, professor of medicine, surgery and physiology at the Medical College of Wisconsin and director of the Endocrine Research Laboratory at Aurora St. Luke’s Medical Center.
“Are the samples being collected properly at the right time of day under the right circumstances with the right method of sampling, whether it’s blood or saliva? How stable are the samples en route from wherever they’re drawn to wherever they’re measured? How is the assay being done and who’s doing it? What is being done with the data? What is the interpretive algorithm being used? What is the sensitivity and specificity? This is standard in the clinical chemistry world, and there has to be a gold standard for whatever they’re doing,” Raff told Endocrine Today.
Even with proper collection and storage, the laboratory processing the sample plays an important role in terms of the accuracy of test results, according to Raff. One indicator of a higher-quality lab is CLIA certification or College of American Pathologists (CAP) accreditation.
“If a lab claims that it’s CLIA-certified, then at least you know they have a minimum of quality control in place because when CLIA comes to inspect, they look at all your quality controls, your performance and your variability. There is a long checklist that you have to pass in order to earn CLIA certification,” Raff said.
Several manufacturers state that they use CLIA-certified and CAP-accredited labs, with one manufacturer noting on its website that this means “they have to meet high standards to obtain both state and federal certifications and submit themselves to regular inspections.” These claims are likely true, Raff noted, as companies would be subject to significant penalties from the Federal Trade Commission for false advertising if they were not.
CLIA certification or CAP accreditation alone, however, does not ensure that information is not lost in translation, according to Andrea Dunaif, MD, Healio | Endocrine Today co-editor and professor and chief of the Hilda and J. Lester Gabrilove division of endocrinology, diabetes and bone disease at the Mount Sinai Health System.
For instance, Dunaif noted that a number of labs offer CLIA-approved testosterone assays that are not done by liquid chromatography-mass spectrometry, as recommended by the Endocrine Society. In some cases, a lab may offer four or five different testosterone assays with different names, but a physician may not be aware of this.
“CLIA certification just means there’s some monitoring of it. It doesn’t mean it’s the ideal methodology [for that patient],” Dunaif said.
An example is anti-Müllerian hormone (AMH) levels, which are assay dependent, Dunaif noted. Because reproductive profiles generally include measurement of both AMH and testosterone for women, use of DTC tests that are not performed using the appropriate process provides patients with inaccurate results.
The importance of context
When addressing two of the major concerns about DTC tests, namely accuracy and the benchmarks used to ensure trustworthy results, physicians may look to agency oversight as one way of gauging the quality of a test. However, the bar for achieving FDA clearance is fairly low, according to Raff.
“Doctors ask, ‘Is that FDA-approved?’ all the time. The terminology is important here because the FDA does not typically ‘approve’ kit assays. The FDA ‘clears’ assays,” Raff said, noting that typically, achieving FDA clearance of a moderate complexity laboratory test does not require as extensive a data set as needed for the approval of a new drug. “I’ve seen some unreliable assays, unrelated to these at-home test kits, that have received FDA clearance.”
Not every DTC testing company has information that addresses FDA clearance, but some state on their websites that they use FDA-cleared tests, and others note that the FDA has not reviewed the statements made on their websites. In any case, the FDA does not review all DTC tests. According to the FDA’s website, the agency generally does not review tests for “non-medical, general wellness or low-risk medical purposes” before becoming available, whereas tests for “moderate- to high-risk medical purposes, which may have a higher impact on medical care, are generally reviewed by the FDA to determine the validity of test claims.”
When the FDA does review a test, it assesses whether the product can accurately and reliably measure what it claims to measure, whether the measurement is predictive of a certain state of health, what the company says about its test and how well it works, and whether the test offers “accurate descriptive information that can be easily understood by a consumer without the involvement of a health care provider.” This last aspect is accomplished by reviewing “the language used to instruct users on collecting the sample and interpreting the test report,” according to the FDA website.
Overall, though CLIA certification, CAP accreditation or FDA clearance may boost confidence in the test results, the quality of the test is almost beside the point, Raff noted.
“The issue is not really the quality of the assays. The issue is what is being done with the results. Is it based on evidence-based medicine? Is it based on comparison to a gold standard?” Raff said. “What you do with the data is the most important thing.”
To this point, the FDA does address the limitations of DTC testing on its website and emphasizes that results should be discussed with a health care provider.
Unfortunately, though, this does not guarantee that a patient will actually visit their physician or that they will even provide proper context for their physicians. For example, Dunaif said that, while monitoring a patient for potential pituitary disease, she received results showing significantly lower prolactin levels than the patient had on previous tests. Assuming that the test had been performed in a reliable central lab as ordered, Dunaif assumed the patient’s condition was improving. It was only in passing conversation, however, that the patient said the test had been performed using a finger stick through a mail-order lab.
“There was nothing on the lab slip I received indicating that a different methodology was used,” Dunaif said, noting that they had not used finger stick to obtain previous samples. “Even in the best of circumstances, [DTC testing] is going to be an additional source of confusion.”
Additionally, many, but not all, of these DTC consumer testing manufacturers note that the results are evaluated by physicians. Some also have a physician available to discuss the results. However, there is a difference between reading results on paper and performing a thorough examination that accounts for the patient’s symptoms, medical history and more, according to experts who spoke with Endocrine Today.
“Patients think that a blood test shows something and that’s the end of the story. Maybe that’s true, but maybe not because not everything in medicine, particularly in endocrinology, is straightforward, and that’s what makes it difficult for patients to understand. It’s why we as endocrinologists exist — so we can help interpret those things that are not straightforward,” Jonathan D. Leffert, MD, FACE, FACP, ECNU, an Endocrine Today Editorial Board Member and managing partner at North Texas Endocrine Center, said in an interview.
Desperate for a diagnosis
DTC testing has gained traction for many reasons, but people’s genuine desire to feel better quickly is one of the main incentives.
Most patients who end up trying these DTC tests, Auchus noted, probably have seen their physicians, undergone the typical screening tests and had normal results but remained convinced that a hormonal imbalance or deficiency was to blame.
Advertising has also likely had a hand in influencing a patient’s perception of symptoms, according to Leffert. For instance, a study published in JAMA in 2017 demonstrated a link between regional exposure to DTC TV advertising about low testosterone, dubbed “low T” in the marketing campaigns, and greater testosterone testing, new initiation of testosterone treatment and initiation of treatment without recent testing among U.S. men.
“Patients can become attached to a particular diagnostic category or diagnosis. As endocrinologists and physicians, we rely as much as possible on a specific diagnostic paradigm, which includes a medical history, a physical evaluation and laboratory testing. That’s what’s missed in a lot of these cases,” Leffert said.
Another issue is these DTC tests are unlikely to yield a definitive diagnosis for multiple reasons. For instance, physicians prefer to measure some hormones, such as estradiol, which is included in several female fertility screening panels, using mass spectrometry because the currently available off-the-shelf assays are less reliable, according to Raff. A finger stick, Raff noted, would not yield enough volume for this type of testing.
Additionally, testing should be more targeted, as not every hormone or biomarker included in these DTC home screening panels is useful for finding a specific diagnosis, according to Auchus.
“You’re running too many tests at one time, so the chances that any one of those is going to be abnormal is very high,” Auchus said.
In the same vein, these test results have to be placed in context, experts told Endocrine Today. For example, according to a 2020 position statement from the American Association of Clinical Endocrinology, a diagnosis of low testosterone requires multiple testosterone levels taken at different times of day to account for natural fluctuations on any given day. Furthermore, in a paper published in Frontiers in Endocrinology, David J. Handelsman, MBBS, PhD, FRACP, noted that blood testosterone should be evaluated alongside blood luteinizing hormone, follicle-stimulating hormone and sex hormone-binding globulin to better capture a patient’s androgen status.
In other cases, such as patients seeking to confirm a diagnosis of so-called adrenal fatigue, there is no gold standard to which the at-home test results can be compared because the endocrine community does not recognize it as a legitimate medical condition, according to the AACE position statement. Although proponents of adrenal fatigue recommend several hormonal assessments, a systematic review published in BMC Endocrine Disorders in 2016 found conflicting results among patients deemed to be fatigued.
“If you’re testing for a nonexistent disease, of course you can say anything you want, and who’s going to prove you wrong?” Raff said.
DTC tests in women’s health
Just as some patients may turn to DTC testing in their quest for a diagnosis, some women hope these at-home tests will enable them to make complex decisions about family planning and reproductive health. In this realm, the home pregnancy test has been a game changer, according to Richard S. Legro, MD, FACOG, professor of obstetrics and gynecology at Penn State College of Medicine.
“Home pregnancy testing has been a boon,” Legro told Endocrine Today. “Patients can detect early and they can come in for treatment, be aware of the pregnancy, alter their lifestyle if they’re potentially engaged in any harmful activities and make us aware of any abnormalities early on.”
Home pregnancy tests, however, are somewhat different from other DTC hormone test options in that they screen only for the presence of a single hormone — human chorionic gonadotropin — in urine that is almost exclusively secreted by a human pregnancy, Legro noted.
“A positive result very much correlates as pregnancy,” Legro said.
Other DTC tests marketed toward women of reproductive age fall short, though. For instance, ovulation predictor kits, which are used to identify a woman’s optimal time for conception by detecting mid-cycle surges in luteinizing hormone in urine, are unreliable in the presence of certain conditions, such as polycystic ovary syndrome, or are prone to false negatives for various reasons, some related to clearance of hormones from urine, Legro noted.
DTC tests claiming to evaluate fertility are perhaps the most problematic, as physician input is essential to understanding what the results actually mean, according to Legro.
“The test that has the greatest commercial abuse right now is probably the use of home testing for ovarian reserve in women,” Legro said, noting that ovarian reserve testing involves the measurement of AMH alone or in combination with other hormones in blood.
“AMH does not predict female fertility. It predicts response to ovarian stimulation. It correlates well with the number of follicles and oocytes that are retrieved at the time of in vitro fertilization, so in that sense, it’s a useful guide for medication dosing and counseling patients about what they can expect from an IVF cycle,” Legro said. “In terms of doing it blindly, it’s useless for telling you what your chance is for having a baby.”
Consequently, physicians usually order testing for ovarian reserve only after a woman receives a formal infertility diagnosis or if a woman is pursuing oocyte cryopreservation. The American College of Obstetricians and Gynecologists also recommended against ovarian reserve testing in otherwise healthy women without a history of infertility in a 2019 policy statement.
These DTC fertility tests may also not be as helpful as women hope, according to a small, ethnographic study of 21 women who pursued DTC ovarian reserve testing in 2018. The study, which was published in Social Science & Medicine in 2019, showed that participants did feel more “in control” of their reproductive future and “empowered” by DTC testing, but they also “experienced varying degrees of certainty about test results and the appropriate next steps to take to confirm fertility status, preserve fertility or conceive, thus suggesting that DTC testing may confound reproductive decision-making,” the researchers wrote.
“Though there may be some benefits to consumers using DTC fertility testing, across the board, participants were left with incorrect assumptions about the power of hormone testing to predict fertility,” study author Moira Kyweluk, PhD, MPH, a former fellow in the department of medical ethics and health policy in the Perelman School of Medicine at the University of Pennsylvania, said in a press release, adding that no test or medical procedure guarantees future fertility, including oocyte cryopreservation.
Finding a place in clinical care
Although DTC at-home hormone tests are problematic in their current form, they may eventually prove useful under certain circumstances, Zilbermint noted.
Ideally, Zilbermint said, all tests would be performed at CLIA-certified or CAP-accredited labs, and physicians would be involved in interpretation of the results. In this scenario, a PCP would diagnose a certain condition after evaluating the patient and their test results, and the patient could perform a quick home test and schedule an appointment with a specialist if the results are abnormal a second time. Then, the home tests could also be used for monitoring. This type of model might be particularly beneficial for conditions such as Hashimoto’s thyroiditis or hypothyroidism because monitoring is relatively simple and the technology is fairly accurate, Zilbermint noted.
“Home testing kits, especially for thyroid conditions, could be part of the future solution to the low number of endocrinologists and could help simplify access to endocrine care,” Zilbermint said. “I believe that this is the future.”
Until home testing kits can be used in that manner, though, physicians should do their best to communicate their role as specialists who can help find an appropriate diagnosis for their patients, according to Leffert.
“On a daily basis, I’m assessing and evaluating laboratory data in light of patients’ symptoms, signs and other conditions, and making diagnoses and giving treatments. That’s the expertise that endocrinologists bring to their fields,” Leffert said. “It’s also important to make sure we’re listening to patients and appropriately evaluating their situations through typical medical means.”
Auchus also emphasized the importance of reviewing the patients’ symptoms, asking why they tried or are considering trying an at-home test, and help them get to the root of their issues.
“Even if you dismiss the test, don’t dismiss the patient,” Auchus said. “They really are having a problem. It may not be medical, but have you have to point them in the right direction.”
- For more information:
- Richard J. Auchus, MD, PhD, can be reached at rauchus@med.umich.edu.
- Andrea Dunaif, MD, can be reached at andrea.dunaif@mssm.edu.
- Jonathan D. Leffert, MD, can be reached at jleffert@leffertmail.com.
- Richard S. Legro, MD, FACOG, can be reached at rlegro@pennstatehealth.psu.edu.
- Hershel Raff, PhD, FAAAS, FAPS, can be reached at hraff@mcw.edu.
- Mihail Zilbermint, MD, MBA, FACE, can be reached at mzilber3@jhmi.edu.
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